Parasitic diseases affect millions of people worldwide with severe social and economic consequences. The protozoan parasites Leishmania major, and Trypanosoma cruzi, cause leishmaniasis and Chagas' disease (CD) respectively. There are several clinical forms of leishmaniasis: visceral leishmaniasis (VL), muco-cutaneous leishmaniasis (MCL), diffuse cutaneous leishmaniasis (DCL) and cutaneous leishmaniasis (CL). As for CD, 15-30% of the people infected with T. cruzi develop manifestations of organ damage, resulting in the cardiac, digestive or nervous forms of chronic Chagas' disease. Currently, there are between 11-18 million individuals infected with T. cruzi, while the overall prevalence of leishmaniasis is 12 million people, with 350 million at risk.
Humans and a wide range of other mammals are usually infected with T. cruzi when the triatomine vector defecates while taking a blood meal. The metacyclic trypomastigote form of the parasite contained in the fecal material is inoculated through the bite wound or mucous membranes. The parasite next invades host cells where it is transformed into intracellular amastigotes. In this stage they proliferate by binary fission and eventually differentiate into trypomastigotes. The host cell finally ruptures releasing the parasites into the circulation where they can invade other cells or be ingested in a blood meal by the insect vector. Leishmania on the other hand, is transmitted by sand flies as metacyclic promastigotes. The proliferative promastigote form then differentiates into the metacyclic form before entering the mammalian host. Once inside the host, the metacyclic form is phagocytosed by macrophages where they differentiate into amastigotes, which proliferate leading to macrophage lysis and further infection of surrounding macrophages.
Despite the advances in understanding the biology of these organisms, most of the drugs still used were developed in colonial times. The current treatment for T. cruzi consists of two nitroheterocyclic derivatives, benzinidazol and nifurtimox. These compounds have severe side effects and since the course of treatment lasts from 1-4 months resulting in many incomplete drug schedules, which leads to the development of resistance. In the case of leishmaniasis, pentavalent antimonials are used throughout most endemic regions; however, they are no longer used in India because of drug resistance. In the 1980s, new formulations of amphotericin B encapsulated in liposomes were developed. This drug is highly effective in both VL and CL; however, its high cost limits the wider use of this drug. Despite the ever-increasing need for safe and effective new drugs, their development has been extremely slow.
Thus there is a need for additional drugs against and treatments for Leishmania major or Leishmania species and T. cruzi. 